The objective of this research program is to study the basic biological processes and mechanisms involved in activation of the fibrinolytic system in health and disease. These studies involve a) the plasma protein plasminogen, its various forms, its mechanism of activation to plasmin by different activators, and the mechanism of inhibition of activation of the zymogen; b) plasminogen with an active site (plasminogen*); c) the mechanism of inhibition of plasmin by various kinds of inhibitors, the preparation of 1-bond and 2-bond cleaved plasmins and kinetic studies on these enzymes, the structure-function relationships of the enzyme and the preparation of various types of heavy(A) and light(B) chains; d) the equimolar plasminogen-streptokinase complex, the transition forms of the zymogen and enzyme, and streptokinase, in the complex, the development of new prototype activators, the development of a common mechanism for interaction of the zymogen and activators; e) the phylogenetic relationships between mammalian and avian zymogens and enzymes; f) the development of new diagnostic methods for studying the components of the fibrinolytic system; and g) the development of methods for studying hereditary disorders of plasminogen. BIBLIOGRAPHIC REFERENCES: Clotting and Lysis in Blood Plasma. L. Lorand and K. C. Robbins, in Physiological and Pharmacological Biochemistry, Vol. 12, MTP International Review of Science, Biochemistry (Series One), pp. 77-100 (1975); Plasminogen and Plasmin. K. C. Robbins and L. Summaria, in L. Lorand (Editor), Methods in Enzymology, Academic Press, New York, in press (1976).